Immunogenicity of a DNA-recombinant hepatitis B vaccine (Engerix B) given at 3, 5 and 11 months of age with a new schedule suitable for mass vaccination programmes

Following the demonstration of a fully satisfactory immunogenic activity of a hepatitis B vaccination protocol consisting of three doses given at the 3rd and 5th months of age with a booster at 11, it was possible to administer this vaccine at the same times as the vaccinations for diphtheria, tetanus and polio which are mandatory in Italy at those ages. A field trial of this protocol in a hyperendemic area near Naples (prevalence of HBsAg about 14%) started on January 1987. The French vaccine, Hevac B, Pasteur, was used. At this time compliance is 99%, and fully satisfactory results both in terms of seroconversion rate (96.3%) and of mean anti-HBs titre (4,352 mIU/ml) two months after the booster dose have been obtained. In this paper we demonstrate that even for a new hepatitis B vaccine prepared by a DNA-recombinant technique (Engerix B, SK & F) recently introduced in Italy, the same schedule can be used. In fact two doses of this vaccine, the first given at three months of age and the second two months later, resulted in a 100% seroconversion rate and a mean anti-HBs titre of 560 mIU/ml. Two months after the booster given at 11 months of age the mean anti-HBs titre was 12,100.     

Adaptability of the anti-hepatitis-B vaccine Recombivax HB to the Piazza protocol for the mass vaccination of newborn infants]

27 healthy babies born to HBsAg, antiHBs and antiHBc negative mothers were given three doses of hepatitis B vaccine "Recombivax HB" (5 micrograms/dose/0.5 ml) at 3, 5 and 11 months of age (Piazza's protocol). AntiHBs response was highly satisfactory. Since both in terms of seroconversion rate and of mean antiHBs titre immunogenicity of other hepatitis B vaccines given at 3, 5 and 11 months of age was already demonstrated, it is possible to conclude that Piazza's protocol is valid for all hepatitis B vaccines available in Italy and will certainly facilitate the compulsory hepatitis B vaccination in infants in Italy.     

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.     

Antibody Response to a Human Diploid Cell Rabies Vaccine

An experimentally killed rabies virus vaccine prepared in a human diploid cell strain (WI-38)—Wyeth rabies vaccine (WRV)—was used by various injection schedules in two separate studies to define more closely in human volunteer subjects an effective vaccination schedule for pre- or postexposure immunization, particularly for donors of rabies-hyperimmune plasma. To permit valid comparisons between our results and those of other workers, antibody levels achieved were expressed in terms of international units (IU) per milliliter of serum. Antibody response of previously nonvaccinated persons were only modest after a single dose of WRV, never reaching a level higher than 0.80 IU/ml over a 56-day testing period. Moreover, antibody was not detected at 0.16 IU/ml before the 14th day, either after a single dose or after two doses given 3 days apart. The best response followed four doses of WRV given within 4 weeks. This schedule resulted in the highest rate of seroconversion to the ≥6 IU/ml antibody level required of potential rabies-immune plasma donors. Giving the first vaccine dose in aluminum hydroxide diluent did not enhance the antibody response. There was a definite suggestion in the various injection schedules that higher and more sustained antibody levels were reached when the interval between the first and second vaccine doses was longest. The greater immunogenicity of WRV as compared with duck embryo vaccine was best demonstrated by the fact that a single booster dose of duck embryo vaccine to previously vaccinated individuals resulted in only a sevenfold antibody rise during the following 56 days, whereas a booster dose of WRV elicited a 69-fold rise. Al(OH)₃ in the first dose of WRV had no effect, but the enhancing effect of a longer interval between vaccine doses was noted once again; 20 of 20 subjects who received three doses of WRV with 4 weeks between doses developed good levels of rabies antibody, and 19 exceeded 6 IU/ml.     

Seroconversion of Hepatitis B Vaccine in Young Children in the Kassena Nankana District of Ghana: A Cross-Sectional Study

Background

Hepatitis B Virus (HBV) infection is an important public health problem that requires high priority efforts towards prevention and control. Active immunization is the single most important and effective preventive measure against HBV infection. As a protective measure, Ghana introduced the mass immunization program against hepatitis B infection in children in 2002 in her Expanded Programme on Immunization (EPI). This study evaluated seroconversion (the point in time when the amount of antibody in the blood becomes detectable) and seroprotection (the point in time when the amount of antibody in the blood is enough to confer protection from the antigen that induced it production) status of children under this mass immunization program and measured their antibody levels five years after immunization.

Materials and Method

200 archived plasma samples of children between the ages of 1–10 years were retrieved from a previous cross-sectional study by researchers from NHRC between 2009 and 2010. Of these, 104 have completed the EPI and were screened for HBsAg. Those found to be HBsAg-seronegative were stratified into three groups according to their age at which the last vaccine was administered. Their anti-HBsAg titer levels were estimated by enzyme linked immunosorbant assay (ELISA).

Results

Two (1.9%) samples were HBsAg seropositive and were excluded from further analyses. 10 more samples were excluded from analyses because they were insufficient. The anti-HBs titers recorded ranged from 1.021 IU/L to 751.64 IU/L indicating a 100% seroconversion rate. In group one (0–6 months), 87.9% were seroprotected. Group two (2-3yrs) had 78.3% seroprotection and group three (3-5yrs) had 41.7% seroprotection. There was no significant difference between group 1 and 2. However, there was a significant difference between group 1 and 3 (p = 0.0137) and between group 2 and 3 (p = 0.0390) respectively. There was no significant difference between male and female children.

Conclusion

All the children who received doses of hepatitis B vaccine at 6, 10 and 14 weeks in the immunization program seroconverted, but their levels of protection waned with increasing years. Booster doses are therefore recommended after 5 years.     

Evaluation of inactivated hepatitis A vaccine in Canadians 40 years of age or more.

OBJECTIVE: To assess the side effects and immune responses after three serial doses of a new inactivated hepatitis A vaccine in people 40 years of age or more. DESIGN: Open, noncomparative trial. SETTING: A hospital, a regional laboratory and public health units in British Columbia. PARTICIPANTS: A volunteer sample of 64 healthy adults aged 40 to 61 years who were seronegative for hepatitis A virus (HAV). All were staff or associates of the health facilities. Exclusion criteria included elevated serum alanine and aspartate aminotransferase levels, a history of liver disease and recent travel to areas of high risk for HAV infection. INTERVENTION: A formalin-inactivated, alum-adsorbed vaccine containing 720 ELISA (enzyme-linked immunosorbent assay) units of antigen from HAV strain HM175 per 1.0-mL dose was injected intramuscularly into the delgoid area. The second and third doses were given 1 and 6 months later respectively. MAIN OUTCOME MEASURES: A detailed diary of any adverse effects for 3 days after each dose. HAV antibody levels in blood samples taken before and 30 days after each dose. RESULTS: All subjects completed the planned series of vaccinations and blood tests; symptom diaries were returned after 190 (99%) of 192 vaccinations. Local symptoms, most often soreness, were reported after 46% of the vaccinations but were mild and usually resolved within 24 hours. A temperature of more than 38.0 degrees C was never reported. Seroconversion occurred in all cases after the two primary doses, and the subjects were still seropositive at 6 months. After the booster dose the geometric mean titre was 2380 mIU/mL, all values being 200 mIU/mL or greater. CONCLUSION: In healthy adults 40 years of age or more the HAV vaccine was well tolerated and highly immunogenic. Final antibody levels were much higher than reported in people passively immunized against HAV with immune serum globulin.     

A modified immunisation schedule for the hepatitis B vaccine Recombivax HB suitable for mass vaccination in childhood.

Following the demonstration of a fully satisfactory immunogenic activity of a hepatitis B vaccination protocol consisting of three doses of Hevac B Pasteur vaccine given at 3,5 and 11 months of age, it was possible to administer this vaccine at the same times as the vaccinations for diphtheria, tetanus and polio which are mandatory in Italy at those ages. We have also shown that both another plasma-derived vaccine, H-B-VAX (MSD), as well as the DNA-recombinant Engerix B (SK&F) are highly immunogenic when given at the same times as the mandatory childhood vaccinations. In this paper we demonstrate that the same schedule can be used for another hepatitis B vaccine prepared by a DNA-recombinant technique, Recombivax HB (MSD) recently introduced in Italy. In fact two doses of this vaccine, the first given at three months of age and the second two months later, resulted in a 100% seroconversion rate and a mean anti-HBs titre of 440 mUI/ml. Although the date are incomplete since the third dose will be given at 11 months of age, we conclude that this hepatitis B vaccine can also be used in the mass vaccination campaigns of infants in Italy, the first of which was initiated in January 1987 in an hyperendemic area near Naples (HBsAg prevalence about 14%). We underline that this mass vaccination campaign is the first in Europe.     

Hepatitis B vaccine: prospects for duration of immunity

The duration of hepatitis B vaccine-induced immunity was studied in a group of 54 seronegative health professionals who received plasma-derived hepatitis B vaccine (Merck's Heptavax) in 1978 and 1979. Five to seven years later, 52 vaccinees received a booster dose of yeast recombinant hepatitis B vaccine (Merck's Recombivax). Of 54 vaccinees, 47 (87 percent) had a favorable anti-HBs response (greater than 10 S/N RIA units) and 7 (13 percent) had low (2.1-10 S/N) or undetectable levels (less than 2.1 S/N) one year after primary immunization. After five to seven years, the anti-HBs values had declined to undetectable levels in 25 percent and to low levels in 23 percent. A booster dose of vaccine induced an anamnestic response in 90 percent of vaccinees by two weeks. The results of this study indicate that persons who respond favorably to primary immunization may be protected for at least seven years.     

Immunisation of neonates at high risk of hepatitis B in England and Wales: national surveillance.

The results of a voluntary programme of immunisation against hepatitis B in neonates at high risk (mother being positive for hepatitis B surface antigen and without hepatitis B e antibody or having had acute hepatitis B late in pregnancy) are reported. The programme was offered in England and Wales from November 1982. Passive immunisation alone was available in the first six months of life until 1985, after which infants received passive and active immunisation from birth; in addition, some infants received passive immunisation for six months followed by a course of hepatitis B vaccine. All but a few infants received the first immunising dose within 48 hours after birth. Blood samples for analysing markers of hepatitis B virus were available at 1 year from 147 of the 223 infants given passive immunisation, 54 of the 72 given passive followed by active immunisation, and 102 of the 155 given passive and active immunisation at birth. At 1 year 11 of the 127 (9%) infants given four or more doses of specific hepatitis B immunoglobulin were positive for hepatitis B surface antigen compared with four of the 20 given three or fewer doses; 11 had levels of hepatitis B surface antibody greater than 50 IU/l. Only one of the 54 infants given passive then active immunisation was positive for hepatitis B surface antigen at 1 year and four infants had low (less than or equal to 50 IU/l) levels of hepatitis B surface antibody. Four of the 102 infants who received passive and active immunisation at birth were positive for hepatitis B surface antigen. Two had received the fill course of vaccine, whereas in the other two vaccination was incomplete or unstated. In 79 of the 89 infants who received a complete course of vaccination the level of hepatitis B surface antibody was known, and 70 had levels at 1 year greater than 100 IU/1. Reactions to immunisation were not severe at any age. The incidence of side effects was 8% for the immunoglobulin, 11% for the vaccine, and 9% when immunoglobulin and vaccine were given together. Wider collaboration in the programme is requested.     

Influenza subunit vaccine: antibody responses to one and two doses of vaccine and length of response,with particular reference to the elderly.

Antibody responses to subunit influenza vaccine prepared against A2/England/42/72 (h3n2) were studied in 69 volunteers aged 60 and over and 231 aged 59 and below over 12 months in 1973 and 1974. After two doses of vaccine seroconversion frequencies and geometric mean haemagglutination-inhibition (HI) titres were higher in the elderly, but no differences were observed between the two groups in the length of their responses. Sixteen (23%) of the elderly volunteers seroconverted only after receiving a second dose of vaccine or seroconverted twice after receiving both doses of vaccine. It was considered justifiable, therefore, to recommend the continuation of a two-dose schedule for patients in a high-risk category. Within 30 weeks of vaccination 87 (29%) volunteers had considerably reduced HI titres (less than 48), which might indicate potential susceptibility to influenza during an epidemic, and the number had risen to 132 (44%) by 50 weeks. It was suggested that high-risk patients should receive annnual vaccination two to four months before the possible epidemic period.     

Recurrent pneumococcal meningitis in a splenectomised HIV-infected patient

Background

Hepatitis B virus infection although preventable by vaccination remains an important health issue throughout the world due to its morbidity, mortality and economical losses. Early seroprotection is desirable for people at high risk of exposure. The aim of this study was to determine whether three-week hepatitis B vaccination (on days 0, 10 and 21) provide seroprotection or not.

Methods

The 120 subjects enrolled into the study were divided into two groups and vaccinated by the classic (months 0, 1, and 2) or the accelerated (days 0, 10, and 21) schedules and antibody response determined on days 30, 60, and 90 and, if below 10 mIU/ml^-1, again on day 180. For each individual in the classic group (B) three subjects were enrolled in the accelerated group (A). Recombinant hepatitis B vaccine (Gen-Hevac B, Pasteur) was given as 20 micrograms intramuscular injections via the deltoid muscle. A booster dose on day 365 was administered for each group. Family members of hepatitis B carriers and volunteer health personnel were enrolled into group A. To the B group only volunteers who wanted vaccination against hepatitis B were included.

Results

After three doses of vaccine, Anti-HBs titers reached protective levels in both groups. The number of vaccinees with seroprotective levels of Anti-HBs (≥10 mIU/ml^-1) on day 30 was 53 (58.9%) in group A and 9 (30.0%) in group B (p < 0.05). On day 60, there was no difference between group A and B, with response rates of 84.4% (n = 76) and 80.0% (n = 24) respectively (p > 0.05). On day 90 there was no difference between group B and group A; with 26 (86.7%) and 79 (87.7%) responders respectively. In both groups those with Anti-HBs levels <10 mIU/ml^-1 attained protective levels by day 180.

Conclusion

In this study, the three-week vaccination provided protective antibody titers within a shorter time compared to the classic schedule. Therefore, in order to provide rapid antibody production against hepatitis B virus, the accelerated vaccination schedule seems to be a good preference.     

Immunogenicity and Safety in Adults of a New Chromatographically Purified Vero-cell Rabies Vaccine (CPRV): a Randomized, Double-blind Trial with Purified Vero-cell Rabies Vaccine (PVRV)

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.     

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects

A total of 250 dentists (53.6% men and 46.4% women), with a mean age of 35.1 +/- 9.8 years, were submitted to serological tests for the diagnosis of hepatitis B (HB)--HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe--using a radioimmunoassay. One or more of these markers were detected in 78 individuals (31.2%) who were excluded from the group to be vaccinated. Of the 172 HB-susceptible individuals, 135 (78.5%) responded to the call and were intradermally injected with three 2 micrograms doses of the Belgian HB recombinant vaccine, applied at an interval of one month between the 1st and 2nd dose and of five months between the 2nd and 3rd dose. A new determination of HB markers carried out 50 days after the 3rd dose showed that 110 (81.5%) individuals had become anti-HBs positive (65.5% good responders and 34.5% poor responders). Mean serum anti-HBs titer of these 110 dentists was 42.4 U S/N, similar in both sexes. The adverse effects analyzed in 106 dentists were: (a) local: pain (12.3%), burning sensation (14.1%), pruritus (25.5%), erythema (28.3%), local heat (18.9%), and a hypochromic spot (32.1%); (b) systemic (4.7%): discomfort in two patients, and fever, anorexia, and asthenia in one patient each. Intradermal administration of a fourth 2 micrograms vaccine dose to 39 dentists (poor or non-responders) increased the total number of anti-HBs-positive individuals from 110 (81.5%) to 114 (84.4%), with the number of good responders increasing from 72 (65.5%) to 85 (74.6%). We conclude that the Belgian recombinant vaccine applied in the scheme used here induces a high rate of seroconversion and causes only mild and transitory adverse effects.     

Effect of a booster dose of serogroup B meningococcal vaccine on antibody response to Neisseria meningitidis in mice vaccinated with different immunization schedules

The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities.     

Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose

Background:

The multicomponent serogroup B meningococcal (4CMenB) vaccine was recently licensed for use in Europe. There are currently no data on the persistence of bactericidal antibodies induced by use of this vaccine in infants. Our objective was to evaluate serogroup B–specific bactericidal antibodies in children aged 40–44 months previously vaccinated at 2, 4, 6 and 12 months of age.

Methods:

Participants given 4 doses of 4CMenB as infants received a fifth dose of the vaccine at 40–44 months of age. Age-matched participants who were MenB vaccine–naive received 4CMenB and formed the control group. We evaluated human complement serum bactericidal activity (hSBA) titres at baseline and 1 month after each dose of 4CMenB.

Results:

Before a booster dose at enrolment, 41%–76% of 17 participants previously vaccinated with 4CMenB in infancy had hSBA titres of 4 or greater against 4 reference strains. Before vaccination in the control group (n = 40) these proportions were similar for strains 44/76-SL (63%) and {"type":"entrez-nucleotide","attrs":{"text":"M10713","term_id":"209124","term_text":"M10713"}}M10713 (68%) but low for strains NZ98/254 (0%) and 5/99 (3%). A booster dose in the 4CMenB-primed participants generated greater increases in hSBA titres than in controls.

Interpretation:

As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40–44 months of age. If 4CMenB were introduced into routine vaccination schedules, assessment of the need for a booster dose would require data on the impact of these declining titres on vaccine effectiveness. ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01027351","term_id":"NCT01027351"}}NCT01027351A vaccine against serogroup B meningococcus has recently been licensed for use in Europe¹ and is being considered for licensure in Canada. This vaccine, known as multicomponent serogroup B meningococcal (4CMenB) vaccine, consists of 3 recombinant proteins: factor H binding protein (fHbp), Neisseria adhesin A (NadA) and Neisseria heparin binding antigen (NHBA) combined with detoxified outer membrane vesicles from the strain responsible for an epidemic of serogroup B meningococcal disease in New Zealand (NZ98/254). Clinical trials of 4CMenB have shown it to be immunogenic against reference strains selected to speciScally express one of the vaccine antigens.^2–6 On the basis of these trials, the approved schedule for infants aged 2 to 5 months is 3 doses given at least 1 month apart, with a booster dose given at 12 to 23 months of age.⁷ The persistence of vaccine-induced antibodies throughout childhood following this booster dose is unknown, but it is particularly relevant because the incidence of invasive serogroup B meningococcal disease in children aged 1 to 4 years is second only to the incidence in children less than 1 year of age.⁸In this study, we assessed the persistence of these bactericidal antibodies in children aged 40–44 months who had previously received either 4CMenB or a vaccine containing the recombinant proteins alone (recombinant protein serogroup B meningococcal [rMenB] vaccine) at 2, 4, 6 and 12 months of age.³ We also assessed the immunogenicity and reactogenicity of a booster dose.     

Evaluation of the immune response to hepatitis B vaccination in children aged 1-3 years in Malatya, Turkey

By the end of 1998, Turkey had launched the routine vaccination of infants against hepatitis B. The purpose of the study is to evaluate the immune response in a sample of vaccinated children aged 1-3 years in the city of Malatya. A total of 210 vaccinated children 12 to 48 months old were selected for the study with 30 cluster sampling in the city of Malatya, Turkey. The children were visited at their homes during January-April 2002. The information on demographic characteristics, family's and child's medical history was gathered, childrens' weight and height were measured and blood samples were taken. Anti-HBs, HbsAg and anti-HBc titers were assayed by micro-ELIZA from the sera. The mean age of the children was 26.3 months, 100 (47.6%) were male and 110 (52.4%) were female. Overall, 203 (96.7%) children had protective anti-HBs levels (> or = 10 IU/l), 0.5% showed evidence of natural infection (with positive anti-HBc and anti-HBs titers), 0.5% had acute or chronic infection (with positive HbsAg and anti-HBc titers) and 2.3% were seronegative. Geometric mean titer of anti-HBs among vaccinated children except those who had positive anti-HBc titers was 138.7 mIU/ml (95% CI:124.7-154.2) and seroconversion rates did not differ by age, sex, anthropometric measurements, time after third dose and place of vaccine administered (P > 0.05). The high seroprotection rate over 95% showed that routine infant vaccination program for hepatitis B was successfully carried out in the city Malatya.     

Immunogenicity and safety assessment of the Cuban recombinant hepatitis B vaccine in healthy adults.

Manufactures of biotechnological/biological products (including vaccines) frequently make changes to manufacturing processes of products both during development and after approval. In our case, a non-inferiority bridging study was carried out to demonstrate that changes in the production plant facilities of Cuban recombinant hepatitis B vaccine, Heberbiovac HB, did not affect the safety and immunogenicity of the vaccine. This controlled, randomized, doubled-blinded trial included 501 volunteers, aged between 20 and 64, who were given three doses of vaccine (20 microg HBsAg/mL) at month 0, 1, and 2. Four lots were evaluated (three corresponding to the new production facilities and a control one produced in the older facilities). One month after the third dose, were observed protective levels of anti-HBsAg in 97% of the subjects that concluded the study with a geometric mean antibody titer (GMT) of 931.18 IU/L. Normal values of body mass index (BMI), the younger ages, and being a female, were significantly related to a good antibody response. The vaccine was well tolerated. Pain at the injection site was the most commonly reported symptom. We conclude that Heberbiovac HB vaccine maintains its characteristics after the modifications carried out in the production plant facilities and both, lot obtained in previous facilities and in the new ones, are comparable in terms of safety and immunogenicity.     

Comparison of one- and two-dose regimens of influenza vaccine for elderly men.

In November and December 1984, 102 male residents of a long-term care facility (mean age 74.6 [extremes 59 and 97] years) received 0.5 ml of trivalent inactivated whole-virion influenza vaccine, containing 15 micrograms of the hemagglutinin of each of A/Philippines/2/82 (H3N2), A/Chile/83 (H1N1) and B/USSR/83. A second dose of the vaccine was administered to a subgroup of 55 randomly chosen subjects 8 weeks later. Serum samples were collected from all the subjects before and 4, 8, 12 and 16 weeks after administration of the first dose and were assayed for hemagglutinin-inhibiting (HAI) antibody to each of the three antigens. At 8 weeks there were significant increases (p less than 0.05) in the geometric mean titre of antibody and in the proportion of subjects with HAI antibody titres of 1:40 or more (except to the B/USSR antigen) in both groups. There were no differences between the groups at 8 weeks or at 16 weeks (8 weeks after administration of the second dose of vaccine) in the frequency of seroconversion, the geometric mean titre or the proportion of subjects with HAI antibody titres of 1:40 or more. Overall, 60%, 32% and 13% of the 102 subjects had titres of 1:40 or more to the A/Philippines, A/Chile and B/USSR antigens respectively at 16 weeks. The results suggest that a second dose of influenza vaccine given 8 weeks after the first does not enhance the immune response in elderly men and that a substantial proportion of this population remains unprotected against infection (having HAI antibody titres of less than 1:40) during the influenza season.     

Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine.

OBJECTIVE--To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN--Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING--Plymouth Health Authority. SUBJECTS--129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES--Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS--All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION--Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster.     

An Open Label Non-inferiority Trial Assessing Vibriocidal Response of a Killed Bivalent Oral Cholera Vaccine Regimen following a Five Year Interval in Kolkata,India

Background

The bivalent killed oral cholera vaccine (OCV) provides 65% cumulative protection over five years. It remains unknown whether a boosting regimen can maintain protection in previously immunized populations. This study examines the immunogenicity and safety of an OCV regimen given five years following initial dosing.

Methodology/Principal Findings

An open label controlled trial was conducted in 426 healthy Indian participants previously enrolled in a large efficacy trial. To assess whether an OCV regimen given after five years can elicit an antibody response equal to that of a primary series, we compared vibriocidal antibody titers in previously immunized participants receiving a two dose booster regimen to participants receiving a primary two dose immunization series. Among participants receiving a two dose primary series of OCV (n = 186), 69% (95% CI 62%-76%) seroconverted. In the intervention arm (n = 184), 66% (95% CI 59%-73%) seroconverted following a two dose boosting schedule given five years following the initial series. Following a single boosting dose, 71% (95% CI 64%-77%) seroconverted. Children demonstrated 79% (95% CI 69%-86%) and 82% (95% CI 73%-88%) seroconversion after primary and boosting regimens, respectively.

Conclusions/Significance

Administration of an OCV boosting regimen elicits an immune response similar to those receiving a primary series in endemic areas. Though a single boosting dose induces a strong immune response, further investigations are needed to measure if these findings translate to clinical protection.